Death by delusion
18 Dec 2018
Written by Christine Carson, PhD
If you believe the apocalyptic rumours (here, here, and here), the rise of antimicrobial, or antibiotic, resistance puts us all in mortal peril of dying from bacterial infections, because antibiotics no longer “work”. Granted, the range and number of bacteria that no longer respond to multiple different families of antibiotics, thereby making the infections difficult to treat, have increased significantly in recent years. This has prompted the predictions of a post-antibiotic era in which bacterial infections will, once again, kill millions of people.
You may think, as long as you stay healthy, you’ll be fine. However, bacterial infections can occur after many activities and procedures regarded as routine such as childbirth, hip replacements, removal of skin moles, invasive dental work, or treatment for cancer. We assume procedures like these can be performed safely because if infections occur afterwards, antibiotics are available to treat them effectively. Enter, antimicrobial resistance. And if the rumour mill is true, our doomsday.
The pandemic that kills hardly anyone
Despite all the hullabaloo about antibiotic resistant bacteria and the havoc they can wreak, in many nations, no-one has officially died because of an infection caused by antimicrobial resistant bacteria. No-one. Not one single person. At least that is the conclusion you could logically draw by looking at death certificates and the causes of death they list.
Skip to the end in La La Land
In the reductionist realm of identifying and documenting causes of death, in which causation is reduced to a clutch of words on a certificate recorded for all posterity, the extinguishment of life due to the ravages of antibiotic-resistant bacteria doesn’t rate, doesn’t exist. It is, if you will, not a valid cause of death. Instead, the focus is on the events that occur as a consequence of unmitigated bacterial infection such as cardiovascular events or multiple irreversible organ failure which culminate in death. This doesn’t mean death as a result of infection with antimicrobial resistant bacteria isn’t happening. It just means it is happening in an administrative vacuum, we are not measuring it and we don’t know the scale of the problem, let alone how to address it.
Don’t ask, don’t know
To be able to see and quantify the scale of the problem, there would have to be useful, comprehensive, baseline data on it. Death certificates would be one way, albeit a rather crude one, to begin capturing that data. Another way would be to record how frequently infections with antibiotic resistant bacteria occur in patients and whether it contributes to death. This is the kind of data that state and territory health departments might collect, although few do. Even if such data are collected, individual regions collect these data in slightly different ways making it difficult to amalgamate the data and get a picture of what is going on nationally and internationally.
The lack of a consensus on the process by which antimicrobial resistance is measured and defined, further complicates the situation. When a patient is diagnosed with a bacterial infection, pathology laboratories test for antimicrobial resistance by performing an antimicrobial susceptibility test, or AST, on bacteria from the patient. Results from ASTs help guide doctors in their antibiotic prescribing decisions, supporting them to make antibiotic choices individualised to that patient’s infection. Better information, faster, helps patients get the antibiotics that stand the best chance of successful treatment. For example, we already know that every hour’s delay in getting the right antibiotic, guided by AST results, to patients, reduces the chances of survival by 7.6% in cases of serious bloodstream infection.
Do judge a book by its (dust) jacket
AST types can be broken down into two main categories: genotypic-based or phenotypic-based tests. The simplest analogy is a book and its cover or dust jacket. The bacterium is the whole book, the words are its DNA and the dust jacket is the way the bacterium presents itself in different environments. Just like dust jackets can be varied in different editions or regional markets, the same bacterium will present differently in different environments – such as when antibiotics are present.
Both approaches have their place.
Genotypic tests detect or analyse bacterial DNA, the words of the book. Genotypic tests are relatively rapid to perform, can be exquisitely sensitive and are designed to target types of resistance we already know about, words we already understand. When bacteria gain new ways of resisting antibiotics, it is like new, unknown words appearing in a book and it can take a while to understand and define them. For genotypic-AST methods, undefined equates to undetectable.
Phenotypic tests detect how a bacterium actually performs under pressure. They appraise how a bacterium behaves, how it presents itself, in the presence of an antibiotic. That is, its cover. Phenotypic methods are generally slower, reasonably sensitive and can detect known and unknown resistance types. Against the current background of rapidly changing and evolving bacterial resistance, this latter feature is significant. AST methods that detect both new and emerging bacterial resistance phenotypes will more reliably predict whether an antibiotic should be used to treat a patient’s infection caused by the test organism.
Unfortunately, the AST methods used differ wildly within and between regions, if they are used at all. The data produced by each system are not interchangeable. They cannot be amalgamated to give a reliable picture of what is going on nationally or be easily compared internationally. There are a few exceptions to this generalisation, but by and large, meaningful national data are hard to come by.
Eyes wide shut
The net effect of all this variation means we know we have a problem but not exactly how big it is. We also haven’t implemented a harmonised way of measuring it with a view to working together for a solution. It is pretty difficult to solve a problem if you don’t know the scale or have the tools and systems in place to measure it. Harmonisation of methods to detect, measure and document antimicrobial resistance must be a priority if we are going to position ourselves to work towards a solution.
Alarmed but not alert
It is both is alarming and ridiculous that we may soon be dying again, in large numbers, from a sore throat, infection after childbirth (puerperal fever), or any number of bacterial infections that featured on our ancestors’ death certificates. That this may happen because there is a lack of solidarity and harmonisation, is mind-numbingly ludicrous. We must address the situation before it gets too bad by identifying, measuring and responding collectively to the issue. The means to collaborate and work towards solutions exists. It is the will that remains to be seen.
Dr Christine Carson is a research microbiologist living and working in Perth, Western Australia. She is interested in all things bacterial, particularly antimicrobial resistance. Christine is part of a research group at The University of Western Australia developing faster, more accurate tests to guide antibiotic therapy choices.